C10-modified artemisinin derivatives: Efficient heme-alkylating agents

被引：42

作者：

Laurent, SAL ^{[1
]}

Robert, A ^{[1
]}

Meunier, B ^{[1
]}

机构：

[1] CNRS, Chim Coordinat Lab, F-31077 Toulouse, France

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2005年 / 44卷 / 14期

关键词：

alkylation; antiviral agents; heme proteins; iron; porphyrinoids;

D O I：

10.1002/anie.200462556

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Chemical Equation Presented) Discussion is reopened regarding C10-substituted derivatives of the peroxide-based antimalarial agent artemisinin (see picture); they are shown to react readily with iron(II)-heme to provide heme-drug adducts in high yields. Substitution or steric hindrance at C10 does not affect the reactivity of the peroxide bond and, thus, does not alter the ability of these powerful antimalarial drugs to alkylate heme. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

收藏

页码：2060 / 2063

页数：4

相关论文

共 26 条

[1] Alkylating capacity and reaction products of antimalarial trioxanes after activation by a heme model [J].

Cazelles, J ;

Robert, A ;

Meunier, B .

JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (03) :609-619

[2] Artemisinins target the SERCA of Plasmodium falciparum [J].

Eckstein-Ludwig, U ;

Webb, RJ ;

van Goethem, IDA ;

East, JM ;

Lee, AG ;

Kimura, M ;

O'Neill, PM ;

Bray, PG ;

Ward, SA ;

Krishna, S .

NATURE, 2003, 424 (6951) :957-961

[3]

Haynes R. K., 2004, ANGEW CHEM, V116, P1405, DOI DOI 10.1016/j.tips.2008.07.004

[4] Highly antimalaria-active artemisinin derivatives: Biological activity does not correlate with chemical reactivity [J].

Haynes, RK ;

Ho, WY ;

Chan, HW ;

Fugmann, B ;

Stetter, J ;

Croft, SL ;

Vivas, L ;

Peters, W ;

Robinson, BL .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (11) :1381-1385

[5]

Haynes RK, 2002, EUR J ORG CHEM, V2002, P113

[6] Mechanism-based design of parasite-targeted artemisinin derivatives: Synthesis and antimalarial activity of new diamine containing analogues [J].

Hindley, S ;

Ward, SA ;

Storr, RC ;

Searle, NL ;

Bray, PG ;

Park, BK ;

Davies, J ;

O'Neill, PM .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (05) :1052-1063

[7] SYNTHESIS AND ANTIMALARIAL ACTIVITY OF (+)-DEOXOARTEMISININ [J].

JUNG, M ;

LI, X ;

BUSTOS, DA ;

ELSOHLY, HN ;

MCCHESNEY, JD ;

MILHOUS, WK .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (05) :1516-1518

[8] Synthesis, stability, and antimalarial activity of new hydrolytically stable and water-soluble (+)-deoxoartelinic acid [J].

Jung, MK ;

Lee, K ;

Kendrick, H ;

Robinson, BL ;

Croft, SL .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (22) :4940-4944

[9]

LAURENT SAL, IN PRESS CHEMBIOCHEM

[10] ANTIMALARIAL ACTIVITY OF NEW WATER-SOLUBLE DIHYDROARTEMISININ DERIVATIVES .2. STEREOSPECIFICITY OF THE ETHER SIDE-CHAIN [J].

LIN, AJ ;

LEE, M ;

KLAYMAN, DL .

JOURNAL OF MEDICINAL CHEMISTRY, 1989, 32 (06) :1249-1252